Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• the functionalization of BBX reagents. (Benzylamino)benziodoxolones, BBXs 2, were prepared according to our reported procedure, via reaction with previously silylated benzylamines (Scheme 2) [4]. Using this methodology, a total of four benziodoxolones (including the new p-fluorobenzylamine

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• building blocks like organohalides can be converted into alkyl radicals by means of photoinduced silane-mediated halogen-atom transfer (XAT) to offer a mild and straightforward methodology of alkylation. In this research, we present a metal-free strategy for the photochemical alkylation of dehydroalanine

• these hydrides, we sought to combine these findings. Herein, we report a photochemical alkylation methodology targeting the olefin moiety of Dha derivatives, conducted in an aqueous solution for the aforementioned bioorthogonal advantages. Results and Discussion Inspired by previously conducted research

•  3), obtaining a slightly elevated yield (67%) compared to compound 3, which was previously formed at a 0.5 mmol scale. Conclusion In conclusion, a photochemical methodology to promote the metal-free alkylation of dehydroalanine derivatives was developed, by means of silane-mediated alkyl bromide

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• reported, providing a novel methodology for the construction of α,β-unsaturated imines [4]. There are different types of α,β-unsaturated imines, such as the acyclic imines aldimines, ketimines, or dienimines, depending on whether they are derived from aldehydes, ketones, or doubly unsaturated ketones

• efficient methodology for synthesizing chiral benzofuran-fused 1,4-dihydropyridines 13 in excellent yields (90–99%) and excellent enantioselectivities (92–99% ee) (Scheme 4). The authors also attempted to perform the reaction using 2-tosylacetonitrile instead of malononitrile. However, in this case, the

• furnish the cycloaddition product 13a. In 2019, Xu’s group published a bifunctional squaramide-catalyzed inverse electron demand aza-Diels–Alder reaction of saccharin-derived 1-azadienes 14 and azlactones 15 [27]. This methodology enables chiral tricyclic derivatives 16 bearing a quaternary amino acid

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• (Scheme 1b). As far as we know, aside from the methodologies mentioned above, there are no other reports on the direct alkylation or fluoroalkylation of these ylide compounds. In line with our ongoing interest in the chemistry of sulfoxonium ylides, we aimed to develop a new alkylation methodology using

• % yield, however, the related benzyl derived ylides gave 3i and 3j in 73% and 61% yields, respectively. Phenyl esters performed well with this methodology (3k,l), but switching to anilide-derived ylides were consistently poorer performing. The N-phenyl ylide derivative reacted to produce 3m in only 50

• Information File 1 for details). This limitation is attributed to the diminished reactivity of these ylides compared to ester and amide-derived sulfoxonium ylides. Having established this new methodology, we then turned our attention to demonstrate additional synthetic applications of this procedure. The

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• for peptide synthesis. Consequently, developing a simple and efficient methodology is still challenging. Our new strategy to synthesize these compounds is based on an aza-Barbier reaction on difluoro- or trifluoromethylated hydrazones. The thus obtained compounds will then be oxidized and cyclized in

• hydrazine [36], allowed the expected compounds 6e and 6f to be obtained in good yields. This methodology was applied to the previous hydrazides 5a–d giving the corresponding compounds 6a–d in similar yields. As expected, no isomerization occurred during the oxidation, leading exclusively to the imine and

• dehydropiperazic acid to act as β or γ-turn is excluded. Interestingly, this novel scaffold rather promotes extended structures. Conclusion To conclude, we have developed a new methodology to synthesize β-analogs of dehydropiperazic acid incorporating fluorinated groups. In order to improve the efficiency of this

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• methodology highlighting compounds 4a (Aβ1‐42 = 65% and AβpE3-42 = 53% of fluorescence) and 4b (Aβ1‐42 = 50% and AβpE3‐42 = 90% of fluorescence) from the first publication and compound 4c (Aβ1‐42 = 74% and AβpE3‐42 = 51% of fluorescence) from the second one (Figure 6). The latter was able to slightly improve

• compounds with high yields (84–92%). The three most promising compounds of the library (13a, 13b, and 13c) were selected for further detailed characterization. In vitro evaluation was performed employing a high-performance liquid chromatography (HPLC)-based methodology, using the fluorogenic histone

• -carboxamide-1,4-benzodiazepin-5-ones when enantiopure (S)-(−)-α-methylbenzylamine and arylglyoxals were used. Thus, a reversal of diastereoselectivity was observed depending on the cyclization methodology employed, the reduction of a nitro group or the Staudinger/aza-Wittig on azide derivatives. This

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• unforeseen new material designs (e.g., redox-active electrooptical materials). Methods pKa measurements in acetonitrile The experimental setup and methodology for the pKa determination of BFC and FIC in acetonitrile was essentially the same as described in detail in previous papers [12][13]. A brief

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• ) cycle and the generation of tert-butylperoxy, tert-butoxy, and perfluoroalkyl radicals [115]. Later, a similar methodology was applied to Co(acac)2-catalyzed difluoroalkylation−peroxidation of alkenes 166 with difluorohaloacetates 167 and TBHP (Scheme 52b) [116][117][118][119][120]. It is assumed that

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a

• remarkable stereoselectivity, a finding elucidated by DFT analysis. These results mark significant progress toward the synthesis of novel fluorinated building blocks. Our team is currently exploring the application of this methodology to amino acid substrates, aiming to contribute further to the burgeoning

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• accepting a wide variety of protective and functional groups, the method creates products with an iodine substituent that is easily accessible for product derivatization. Moreover, it is a convenient methodology for both N-arylation and O-arylation. The arylation of amines 38 was achieved in acetonitrile as

• high conversions (83–93%) in 1–20 hours. Purification by HPLC yielded the isolated oxime conjugates in excellent amounts. This methodology presents a promising approach for the late-stage variation of proteins and peptides, offering versatility and efficiency in aqueous environments. In addition to

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• being explained by a tedious purification. Interestingly, the methodology was successfully applied to the functionalization of aliphatic hydrazones 1s and 1t and even the hydrazone derived from citronellal 1u. The method was functional group-tolerant to various functional groups (nitro, CN, ester

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• trichloroacetimidate failed, due to competing formation of orthoester-like amide acetals during the reaction with 1b. We then focused our work on an alternative synthetic approach (vide infra). In 2021, Pfretzschner and Unverzagt reported the application of our methodology to the synthesis of indigo-N-glucoside 7c

• the methodology described above, acceptor-substituted isatin-N-glucosides 23b–f and xyloside 23g were prepared in 25–83% yields (Scheme 17) [24]. All products were formed as the β-anomers. The yield of product 23e derived from m-fluoroaniline was significantly higher as compared to product 23c derived

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• various nucleophilic reagents further hampers the reactivity of coumarins. Xu, Peng and Feng et al. [70] introduce a groundbreaking dual remote enantioselective copper-catalyzed yne-allylic substitution methodology tailored specifically for coumarins (Scheme 21). This innovative approach facilitates the

• -catalyzed protocol for the vinylogous yne-allylic substitution utilizing coumarins as substrates (Scheme 22). The methodology stands out for its exceptional regio and enantioselectivities, while employing readily available starting materials and mild reaction conditions, showcasing the robustness of the

• shuttling (Scheme 53, 51a–k). Furthermore, they established a Cu-catalyzed asymmetric multicomponent reaction for yne-allylic substitution, seamlessly integrating 13C-labeled CO2 into enantiomerically pure products (Scheme 54, 51a, 51c, 51f, 51g). This methodology enabled the synthesis of diverse, high

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• with Hanessian stain (dipping into a solution of (NH4)4MoO4·4H2O (21 g) and Ce(SO4)2·4H2O (1 g) in H2SO4 (31 mL) and H2O (469 mL) and warming). Rf were measured after an elution of 7–9 cm. Column chromatographies were done with the "flash" methodology using 220–400 mesh silica or 150 mesh aluminum

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• and Suzuki–Miyaura cross-coupling reactions followed by Brønsted acid-mediated cycloisomerisation. The developed methodology tolerates various functional groups and leads to moderate up to quantitative yields of the final products. The impact of different functional groups on the optical properties

• investigation or modulation of desired properties. Conclusion In summary, we have developed the synthesis of novel polycyclic uracil-based compounds. Careful optimisation of the reaction conditions led to the isolation of the desired products in excellent to moderate yields. The developed methodology tolerates

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• substitution (SNAr) reaction between 2-chloro-6,7-dimethoxy-4-sulfonylquinazoline derivatives and NaN3, while the second involved an SNAr reaction between 2,4-dichloro-6,7-dimethoxyquinazoline and alkyl/arylsulfinates, followed by substitution with NaN3. Using this developed methodology, the adrenoblockers

• terazosin and prazosin were successfully synthesized. Oliveira Jr. et al. developed a new methodology for the asymmetric synthesis of β-aryl-γ-lactam derivatives with very good yield and enantioselectivity [16]. This was achieved through a palladium-catalyzed Heck–Matsuda desymmetrization of N-protected 2,5

• -dihydro-1H-pyrroles using aryldiazonium salts and (S)-PyraBox, followed by sequential Jones oxidation. They showcased their methodology by preparing both (R)-rolipram and (R)-baclofen hydrochloride. Tóth et al. reported the design and synthesis of new analogues of HeE1-2Tyr, a nonnucleoside SARS-CoV-2

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• bonded to the nitrogen atom of the aniline substrate. The methodology showcases a broad scope for carboxylic acids and demonstrates multiple examples of LSF of pharmaceuticals and natural products. The proposed mechanism begins with the formation of Ru(II) diacetate through ligand exchange between the

• undivided cell using a boron-doped diamond (BDD) anode and a platinum cathode at constant current, resulting in 1,4-dicarbonyls with yields up to 91% and enantiomeric excesses (ee) greater than 99%. This methodology was demonstrated in the LSF of two complex natural product derivatives: a β-ionone

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• rearrangement reaction [7][8][9][10][14][15]. With the established photo-flow platform and optimized conditions, we were interested in investigating the scope of this methodology using several substituted furfuryl alcohol substrates (2a–p) which were subjected to the Achmatowicz reaction utilizing our photo

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• -diastereoisomer was favored. In this study, enantiopure 3-(1’-(tert-butyldimethylsilyl)ethyl)-β-lactams 10c–f were also tested. Products 12c–f were obtained with moderate to good yield, underscoring the feasibility of the methodology for the C3-substituted β-lactam moiety. The configuration at the newly formed

• thiophenolate. Conclusion To conclude, we have employed a photoredox methodology to access clavam and pyrrolyloxazole intermediates, showing the possibility of using the nucleophilic nitrogen atom of β-lactams under photoredox conditions. The acridinium catalyst IV was able to oxidize the C=C double bond

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• as a key methodology in the synthesis of alkaloids and natural products with 4-, 5- and 6-membered cyclic amine motifs. Initially reliant on stoichiometric reagents, synthetic chemists predominantly used N-substituted chiral imines, organometallic chiral reagents and achiral reagents with an

• almost exclusively produced anti-homoallylamine 7, with (E)-6 being slightly more efficient. This was explained by the reaction switching from the chair-like TS in (E)-crotylation to the boat-like TS in (Z)-crotylation. The developed methodology was successfully applied for the total synthesis of

• as an activator. Interesting examples of a direct asymmetric allylation of indoles 15 (Scheme 4) and 3,4-dihydroisoquinolines 22 (Scheme 5) with geranyl- and prenylboronic acids 14 in the presence of BINOL derivatives were reported by Szabó [25]. In the case of 3-methylindole, the methodology enabled

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• this research gap by introducing an effective methodology for generating enantiomerically enriched products, thereby expanding the scope of applications and contributing to a deeper understanding of stereoselective covalent catalysis, particularly in the field of mechanochemistry. Results and

• for unconventional reaction pathways by exploiting kinetic energy to surpass equilibrium constraints. This methodology presents several advantages over conventional solvent-based approaches, including the potential for diverse product formation with limited substrates and the development of

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• , Tucson, Arizona, 85721, USA 10.3762/bjoc.20.195 Abstract The utility of bio-isosteres is broad in drug discovery and methodology herein enables the preparation of deuterium-labeled products is the most fundamental of known bio-isosteric replacements. As such we report the use of both [D1]-aldehydes and

• Leuckart–Wallach methodology developed herein, deuterated aldehydes can be converted into [D2]-isocyanides. The optimized conditions for this reaction are summarized below (Table 1). It is important to note that 1 equivalent of formamide and excess [D2]-formic acid (Table 1, entry 2) leads to increased

• modification of 1d, representative of the large swath of chemical space accessible by Ugi-deprotect-cyclize (UDC) methodology, gave the dihydroquinoxaline 1g in good yield with high deuterium retention [29][30][31][32]. The catalytic three-component Ugi reaction was first reported by List in 2008 [33][34] and

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• ) are the key methodology to access valuable heterocycles for medicinal chemistry projects. The classical Biginelli reaction (1893) is an acid-catalyzed, three-component reaction between an aldehyde, β-ketoester, and urea that produces 3,4-dihydropyrimidin-2(1H)-ones, also known as DHPMs (Scheme 1A

• -4,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidine-2(3H)-one/thione/selenone 5,5-dioxides and some of their derivatives. Furthermore, this methodology was successfully applied for the synthesis of the SO2-containing analogue of the anticancer drug-candidate enastron (SO2 vs C=O), and we believe a multitude

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern

• methodology demands that all sequences have to be performed in the same reaction vessel; neither intermediate work-up, filtration of byproducts, nor solvent exchange by evaporation falls within the scope of MCR. Therefore, this review aims to present and discuss the concepts of ring-forming MCR syntheses of

• necessary [73]. Most advantageously, this methodology tolerates many polar functional groups and allows access to pyrazole libraries from simple starting materials (alkynes, acid chlorides, hydrazines) in good to excellent yield. Notably, pyrazoles 102 and 103 demonstrate intense luminescence both in